Hydrochloric Acid → HCID 178446270, compound

HRID 2406924Notes

Reaction equation

HRID 2406924 reaction equation
[CH3:1][CH:2]([CH3:32])[CH2:3][CH:4]([NH:21][C:22]1[N:27]=[CH:26][C:25]([C:28]([O:30]C)=O)=[CH:24][N:23]=1)[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.[Li+].[OH-].Cl.C(N1C=CN=C1)(N1C=CN=C1)=O.C(N(C(C)C)CC)(C)C.[NH2:57][C:58]1[NH:62][N:61]=[N:60][N:59]=1>O1CCCC1>[CH3:32][CH:2]([CH3:1])[CH2:3][CH:4]([NH:21][C:22]1[N:27]=[CH:26][C:25]([C:28]([NH:57][C:58]2[NH:62][N:61]=[N:60][N:59]=2)=[O:30])=[CH:24][N:23]=1)[C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:20])[F:19])=[CH:15][CH:16]=2)=[CH:9][CH:10]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 67981158HCID 67981158, compoundHCID 178509299HCID 178509299, compound

Product 1

HCID 178446270HCID 178446270, compoundYield 4.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)pyrimidine-5-carboxylate (Example 1.4, step A) (0.220 g, 0.496 mmol) in anhydrous tetrahydrofuran (8 mL) was added 2M LiOH (8 mL) slowly at 0° C. The mixture was heated to 50° C. and stirred for 48 hours. The mixture was neutralized with 1N HCl and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in N,N-dimethylformamide (20 mL) and 1,1′-carbonyldiimidazole (123 mg, 0.757 mmol) and diisopropylethylamine (113 mg, 0.873 mmol) were added. The mixture was stirred for 30 minutes at 80° C. 5-Aminotetrazole (148 mg, 1.75 mmol) was then added to the reaction mixture. The resulting mixture was stirred overnight at 80° C. The mixture was quenched with water and extracted with ethyl acetate (3×10 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by preparative HPLC gave (+/−)-2-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)-N-(1H-tetrazol-5-yl)pyrimidine-5-carboxamide (11 mg, 3.8%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.87 (s, 2H), 7.78 (d, 2H), 7.26 (d, 2H), 7.64 (d, 2H), 7.51 (d, 2H), 5.32-5.26 (m, 1H), 1.95-1.89 (m, 1H), 1.78-1.65 (m, 2H), 1.01 (d, 3H), 0.99 (d, 3H) ppm. MS (M+1): 495.1.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (20 mL)
  6. stirringThe mixture was stirred for 30 minutes at 80° C
  7. stirringThe resulting mixture was stirred overnight at 80° C
  8. customThe mixture was quenched with water
  9. extractionextracted with ethyl acetate (3×10 mL)
  10. washThe organic layer was washed with brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-ad4f43eadd184ad0abe23299b543be4f
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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